1. Field of Invention
The present invention relates to a long-lasting collagen and its manufacturing method, and more particularly to a method of producing a collagen by adding γ-polyglutarmic acid (γ-PGA) to the collagen and going through two crosslinking processes to obtain the long-lasting collagen. The invention not only increases the storage time of the collagen in human body, but also achieves a better biocompatibility and provides a higher value for practical applications.
2. Description of Related Art
As we get older, our skin ages and loses its charm and healthy glow, causing wrinkles and tough inelastic skins, since the metabolic capability of dermis under the skin reduces with age, and the dermis is a main factor of the elasticity of skin. Reduction in the metabolic capability of skin will lead to skin aging, and thus various different rejuvenation methods are developed and available in the market. Among these rejuvenation methods, facial filler gives the best effect so far, and facial filler can be divided into two main types of materials: a synthetic material and a natural material. The synthetic material includes: silicone, hydroxyapatite (HAP), polylactic acid (PLA), polymethyl methacrylate (PMMA) and hydroxyethylmethacrylate (HEMA), etc. The natural material includes: botox (BT), autologous fat, collagen and hyaluronic acid (HA), etc.
However, the synthetic facial filler has the following drawbacks:
1. Silicone exists permanently in human body after being injected into the human body and it will cause long term inflammation and granulomas, and thus the silicone must be removed by operation. In addition, silicon may migrate due to gravitational force, and thus U.S. Food and Drug Administration (FDA) prohibits applying silicon into human beings by laws.
2. In a hydroxyapatite (HAP) material such as Radiesse, the only facial filler meeting the laws and regulations set forth by the U.S. Food and Drug Administration (FDA). Although HAP can be maintained for 2 to 5 years, nodule may occur sometime, particularly at the positions of mouth and lip, and it gives a bad look.
3. Poly l-lactic acid (PLLA) is generally used as an injection material. Although PLLA has been approved by U.S. Food and Drug Administration (FDA), granulomas may still occur, and PLLA has the highest frequency of occurrence of granulomas among all facial fillers.
4. Polymethyl methacrylate (PMMA) comes with an excellent biocompatibility, but it cannot be degraded in human body and becomes a bio-accumulative substance. Although PMMA is a permanent implantation material, granulomas also occurs easily, and thus many countries have banned the use of polymethyl methacrylate (PMMA) for hypodermic injection.
5. Hydroxyethylmethacrylate (HEMA) has a drawback similar to that of the polymethyl methacrylate (PMMA), but it contains a hydroxyl radical (—OH), and thus its elasticity is enhanced after being applied. However, PMMA will be hardened as time goes by.
In summation, the shortcomings of the synthetic facial filler material reside on its causing serious inflammations and having major side effects on human bodies.
Further, the natural facial fillers also have the following drawbacks:
1. Botox (BT) disables some of the biological functions of nerves and muscles by holding back the release of acetylcholine to achieve the effect of removing dynamic wrinkles, but botox (BT) also disables some of the biological functions of muscles, and the muscles will be degenerated after a period of time, and the facial expression of a patient will be unnatural when smiling. As the muscle activity is reduced, patients have to massage the injecting position everyday. In addition, researches reports show that there is 1% of fatal risk for an overdose of botox (BT).
2. Autologous fat is made of a material coming from a patient's autologous fat, and thus the biocompatibility is very high, but the time for the autologous fat to be remained in human varies greatly due to the fat source and the individual difference of the patient, and the time varies from months to years. On the other hand, the autologous fat has larger particles that cannot fill wrinkles or small lines in a small area, and thus the effect and range are very limited.
3. There are different collagens including human collagens, cadaveric collagens, bovine collagens and porcine collagens, etc, wherein the bovine collagen has been used for more than 20 years, and approved by the U.S. Food and Drug Administration (FDA). As mad cow disease existed in both animals and humans explodes and has the risk of infection. Although human collagen has passed the approval of the U.S. Food and Drug Administration (FDA), human collagen is not available easily, and its price is higher than other materials. The cadaveric collagen is also not available easily as the human collagen, and the particle size is larger than the human collagen falling within a range of micrometer (μm) and millimeter (mm) due to the factor of cultivation environment, and thus a thicker and larger needle is needed and it will cause additional pain to patients.
4. Since hyaluronic acid (HA) is a polysaccharide composed of two monomers (such as N-acetyglucosamine and D-glucuronic acid) that can go through a complete metabolism, but the structure of the monomer (such as N-acetyglucosamine) is very close to heparin, such that if there is a wound, the monomer (N-acetyglucosamine) will be used for filling, and the quantity of hyaluronic acid (HA) will be reduced. Since hyaluronic acid (HA) can enhance the combination of matter under the dermis and cannot make the skin elastic, therefore it is necessary to avoid the wound from being pressed by external forces and further hurting the wound after the implantation. On the other hand, the movement of muscles accelerates the absorption of hyaluronic acid (HA), and thus patients have to avoid excessive facial expressions.
In summation of the foregoing materials of the natural and synthetic facial fillers, the level of inflammation caused by collagens is the lowest, and thus collagens can be used extensively, but they still have the following drawbacks:
1. The time of collagens remained in human body is short, and uncrosslinked collagens will be degraded and absorbed in human body within three months, and collagens crosslinked by a crosslinking agent such as glutaraldehyde can remain a human body for six months, which is still too short, so that patients have to apply an injection for the supplement frequently, and it causes tremendous inconvenience.
2. Collagens are biological poisonous, and the collagens crosslinked by glutaraldehyde have a high concentration of remained glutaraldehyde, which is biologically poisonous and harzardous to human health.
Obviously, the conventional collagens still have many drawbacks and require further improvements.